Assessment of the efficacy of commercially available and candidate vaccines against a pandemic H1N1 2009 virus.

BACKGROUND: The emergence and global spread of the pandemic H1N1 2009 influenza virus have raised questions regarding the protective effect of available seasonal vaccines and the efficacy of a newly produced matched vaccine. METHODS: Ferrets were immunized with the 2008-2009 formulations of commercially available live attenuated (FluMist; MedImmune) or split-inactivated (Fluviral; GlaxoSmithKline) vaccines, a commercial swine vaccine (FluSure; Pfizer), or a laboratory-produced matched inactivated whole-virus vaccine (A/Mexico/InDRE4487/2009). Adaptive immune responses were monitored, and the animals were challenged with A/Mexico/InDRE4487/2009 after 5 weeks. RESULTS: Only animals that received the swine or matched vaccines developed detectable hemagglutination-inhibiting antibodies against the challenge virus, whereas a T cell response was exclusively detected in animals vaccinated with FluMist. After challenge, all animals had high levels of virus replication in the upper respiratory tract. However, preexisting anti-pandemic H1N1 2009 antibodies resulted in reduced clinical signs and improved survival. Surprisingly, FluMist was associated with a slight increase in mortality and greater lung damage, which correlated with early up-regulation of interleukin-10. CONCLUSIONS: The present study demonstrates that a single dose of matched inactivated vaccine confers partial protection against a pandemic H1N1 2009 virus, and it suggests that a higher dose or prime-boost regimen may be required. The consequences of mismatched immunity to influenza merit further investigation.

Virulence differences of closely related pandemic 2009 H1N1 isolates correlate with increased inflammatory responses in ferrets.

Several early pandemic H1N1 influenza isolates cause severe disease in different animals models, while most strains result in mild clinical signs similar to seasonal influenza. In this study, the pathogenesis of the virulent Mexican isolate A/Mexico/InDRE4487/2009 and a mild Canadian isolate A/Canada-AB/RV1532/2009 was compared in ferrets. These viruses differed at nine residues, none of which has been previously identified as virulence factor. The Mexican isolate caused more severe disease and higher mortality, and reached higher peak nasal wash titers. Both viruses grew similarly in the respiratory tract, but only the virulent virus was detected in the gut after day 3. During the acute phase, both strains caused similar lung pathology, however the Mexican isolate induced severe inflammation even after virus clearance. This virus was also associated with a rapid and sustained induction of inflammatory cytokines, indicating that early dysregulation of the host response contributes importantly to the disease outcome.